The purpose of this study is to compare the blood levels, absorption, and breakdown of lamivudine (3TC), nevirapine (NVP), and stavudine (d4T) in a fixed-dose tablet to that of the individual liquid formulations of the same anti-HIV drugs in HIV infected Thai children.

A Phase I/II Comparative Pharmacokinetic Study of the Fixed-Dose Combination (FDC) of Stavudine (d4T), Lamivudine (3TC), and Nevirapine (NVP) as GPO-VIR Pediatric Chewable Tablets Versus the Individual Liquid Formulations in HIV Infected Children 6 Months and Older to Less Than 13 Years of Age in Thailand

Dosage dependent on weight. More information on this criterion can be found in the protocol.

Drug: Nevirapine

Dosage dependent on weight. More information on this criterion can be found in the protocol.

Drug: Stavudine

Dosage dependent on weight. More information on this criterion can be found in the protocol.

Detailed Description:

The Thai Ministry of Public Health strives to provide the HIV infected people of Thailand with affordable antiretrovirals (ARVs). A fixed-dose combination tablet of 3TC, NVP, and d4T is recommended as first-line treatment in HIV infected adults in Thailand. There has been no similar product developed for children for several reasons: pediatric dosing is based on age, weight, or body surface area; developmental changes may influence the bioavailability and pharmacokinetics (PK) of ARVs; and medication adherence may also be a problem. The purpose of this study is to gather bioavailability and PK data in children taking a fixed-dose tablet of 3TC, NVP, and d4T. This information will then be compared to the bioavailability and PK of the individual liquid formulations of these ARVs.

This study has two stages. Stage 1 will last a minimum of 4 weeks; Stage 2 will last a minimum of 8 weeks. In Stage 1, patients will be randomly assigned to one of two arms. Arm A will receive the fixed-dose tablet twice daily for 2 weeks, then switch to the individual liquid formulations twice daily for 2 weeks. Arm B will receive the individual liquid formulations twice daily for 2 weeks, then switch to the fixed-dose tablet twice daily for 2 weeks. To encourage medication adherence, study staff will make home visits and phone calls to each patient's parent or guardian the first week of each treatment regimen. Medical history, a physical exam, and urine collection will occur on Days 11 and 25. Also on Days 11 and 25, patients will be admitted to the hospital to ensure 100% medication adherence and to provide blood for PK studies.

Stage 1 patients are not eligible for Stage 2. In Stage 2, patients will be stratified by body weight, then randomly assigned to one of two arms. Arm A will receive the fixed-dose tablet twice daily for 4 weeks, then switch to the individual liquid formulations twice daily for 4 weeks. Arm B will receive the individual liquid formulations twice daily for 4 weeks, then switch to the fixed-dose tablet twice daily for 4 weeks. To encourage medication adherence, study staff will make home visits and phone calls to each patient's parent or guardian the first week of each treatment regimen. Medical history, documentation of direct observation of therapy (DOT), a physical exam, and urine collection will occur on Days 25 and 53. Also on Days 25 and 53, patients will be admitted to the hospital to ensure 100% medication adherence and to provide blood for PK studies.

Eligibility

Ages Eligible for Study:

6 Months to 13 Years

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria for Stages 1 and 2:

HIV infected

On a highly active antiretroviral regimen (HAART) including NVP and 2 nucleoside reverse transcriptase inhibitors and receiving a maintenance of NVP for at least 4 weeks prior to study entry and taking the current recommended oral dose every 12 hours

Willing to swallow or chew study drugs

Willing to be hospitalized for the 12 hour PK studies

Willing to use acceptable forms of contraception

Parent or guardian willing to provide informed consent

Inclusion Criteria for Stage 1:

Between 12 to 30 kg (26.5 to 66.1 lbs)

Inclusion Criteria for Stage 2:

Between 6 to 30 kg (13.2 to 66.1 lbs)

Exclusion Criteria:

Certain abnormal laboratory values

Require certain medications

Grade 2 or greater vomiting within 30 days prior to study entry

Grade 2 or greater diarrhea within 30 days prior to study entry

History of immunological failure (CD4 percentage decrease of more than 30% within a 6-month period for children 6 years or younger OR CD4 cell count decrease of more than 30% within a 6-month period for children older than 6 years)

Current treatment for acute serious bacterial, viral, or opportunistic infection

History of dose-limiting toxicity requiring treatment discontinuation of any of the study drugs

Treatment with immune modulators or myelosuppressive, neurotoxic, pancreatotoxic, hepatotoxic, or cytotoxic drugs within 30 days prior to study entry. Patients who have received therapeutic vaccines are not excluded.

Treatment with experimental drugs within 30 days of study entry

Acute inflammation of the liver

Chemotherapy for active cancer

Any clinically significant diseases other than HIV infection or clinically significant findings that, in the investigator's opinion, may interfere with the study

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Please refer to this study by its ClinicalTrials.gov identifier: NCT00312091